tbuckley/cabot-search huggingface dataset:
Incidental Detection of 68Ga-DOTA-RGD-2 Uptake in Uterine Fibroid
Authors: Ritanshu Solanki, Bhagwant Rai Mittal, Rajender Kumar, Harmandeep Singh, Aman Sharma
Journal: Clinical Nuclear Medicine (2023)

Abstract Uterine fibroids are benign tumors originating from the smooth muscle cells of the myometrium seen in approximately 20%–50% of women of reproductive age. The Arg-Gly-Asp (RGD) binds to αvβ3 integrin expressed on the surface of angiogenic blood vessels or tumor cells. 18 F-FDG PET/CT has been used to evaluate uterine fibroids, with moderate 18 F-FDG uptake. However, angiogenesis imaging in uterine fibroids has not been evaluated. The present case presents a rare finding of RGD uptake in the uterine fibroid on 68 Ga-DOTA-RGD-2 PET/CT in a patient who underwent angiogenesis imaging for left ankle joint pain and swelling.
Colorectal Adenocarcinoma Mimicking Neuroendocrine Neoplasia on 18F-FDOPA PET/CT
Authors: Aurélie Moreau, Vanina Isnardi, Thomas Mognetti, Alexandra Meurgey, David Kryza
Journal: Clinical Nuclear Medicine (2023)

We present a case of a 48-year-old woman who had previously undergone surgical resection for bladder paraganglioma. An 18F-FDOPA PET/CT scan performed for suspected colorectal paraganglioma showed intense colorectal uptake associated with adenopathy. Histological examination did not support the presence of a neuroendocrine tumor but instead confirmed the presence of moderately differentiated colorectal adenocarcinoma. Colorectal adenocarcinoma belongs to the list of nonneuroendocrine false-positive tumors that can be detected using 18F-FDOPA. Therefore, a morphological analysis is important. Thus, 18F-FDOPA may be a marker for the aggressiveness of colorectal adenocarcinoma.
Oxylipin transport by lipoprotein particles and its functional implications for cardiometabolic and neurological disorders
Authors: Nuanyi Liang, Brian A. Harsch, Sitong Zhou, Alison Borkowska, Gregory C. Shearer, Rima Kaddurah-Daouk, John W. Newman, Kamil Borkowski
Journal: Progress in Lipid Research (2023)

Lipoprotein metabolism is critical to inflammation. While the periphery and central nervous system (CNS) have separate yet connected lipoprotein systems, impaired lipoprotein metabolism is implicated in both cardiometabolic and neurological disorders. Despite the substantial investigation into the composition, structure and function of lipoproteins, the lipoprotein oxylipin profiles, their influence on lipoprotein functions, and their potential biological implications are unclear. Lipoproteins carry most of the circulating oxylipins. Importantly, lipoprotein-mediated oxylipin transport allows for endocrine signaling by these lipid mediators, long considered to have only autocrine and paracrine functions. Alterations in plasma lipoprotein oxylipin composition can directly impact inflammatory responses of lipoprotein metabolizing cells. Similar investigations of CNS lipoprotein oxylipins are non-existent to date. However, as APOE4 is associated with Alzheimer's disease-related microglia dysfunction and oxylipin dysregulation, ApoE4-dependent lipoprotein oxylipin modulation in neurological pathologies is suggested. Such investigations are crucial to bridge knowledge gaps linking oxylipin- and lipoprotein-related disorders in both periphery and CNS. Here, after providing a summary of existent literatures on lipoprotein oxylipin analysis methods, we emphasize the importance of lipoproteins in oxylipin transport and argue that understanding the compartmentalization and distribution of lipoprotein oxylipins may fundamentally alter our consideration of the roles of lipoprotein in cardiometabolic and neurological disorders.
Enterovesical Fistula in a Lymphoma Patient Revealed by FDG PET/CT With an Oral Contrast Agents
Authors: Linlin Guo, Guohua Shen
Journal: Clinical Nuclear Medicine (2023)

Abstract A 60-year-old man with colonic diffuse large B-cell lymphoma was referred for FDG PET/CT for initial staging. He was suspected of enterovesical fistula. After oral administration, large amounts of contrast agents accumulated in the bowel lumen and leaked into the bladder through a well-marked fistulous tract. Corresponding to the fistula, a linear pattern of FDG uptake extended from the bladder into the colonic lumen, and the measured SUV max inside the lesion was as high as that of the urinary bladder. Cystography confirmed the presence of the enterovesical fistula.
FAPI Uptake in Gallbladder Is It Normal Biodistribution?
Authors: Hossein Behnam-Manesh, Abtin Doroudinia, Mohadeseh Bayat, Mehrdad Bakhshayesh Karam, Babak Salimi, Marzieh Nejabat, Payam Mehrian
Journal: Clinical Nuclear Medicine (2023)

Radiolabeled fibroblast activation protein inhibitors (FAPIs) have been extensively used in different types of cancers, although not yet FDA approved. Normal patterns of FAPI biodistribution have been investigated, and it is known that FAPI is expressed in nonmalignant pathophysiological lesions, characterized by tissue remodeling such as atherosclerosis, arthritis, and scar/fibrotic tissues. In this interesting image, we are presenting the accumulation of 68Ga-FAPI in the gallbladder. This finding could be related to a normal distribution of the radiotracer as a physiologic finding. This is a potentially important finding as FAPI may be used as theragnostic agent in the future.
Primary Extranodal Nasal-Type Natural Killer/T-Cell Lymphoma of Lower Limb Muscles on 18F-FDG PET/CT
Authors: Chuan Li, Xianwen Hu
Journal: Clinical Nuclear Medicine (2023)

Abstract Extranodal nasal-type natural killer/T-cell lymphoma may arise anywhere outside the lymph nodes, predominantly including the nasal cavity, nasopharynx, oropharynx, upper respiratory tract, gastrointestinal tract, skin, testes, and salivary glands, whereas primary tumor arising in muscle is rarely documented. We report FDG PET/CT findings of primary extranodal nasal-type natural killer/T-cell lymphoma in the muscles of the right lower limb in an 82-year-old man.
False-Positive Metastatic Disease Due to Bilateral Ectopic Adrenal Tissue
Authors: Edward Li, Rahul Anand Kumar, Jeffrey Chen, Owen Kang, Robert Mansberg
Journal: Clinical Nuclear Medicine (2023)

Abstract A 60-year-old man was referred for staging of prostate cancer. Initial CT scan demonstrated soft tissue lesions in bilateral renal hila, which demonstrated mild 68 Ga-PSMA avidity and moderate FDG avidity on sequential PET scans suspicious for malignancy. Biopsy confirmed adrenal cortical tissue. This case highlights an exceedingly rare occurrence of ectopic adrenocortical tissue in both renal hila.
FDG PET/CT Demonstrated Unilateral Striatum Hypometabolism in a Case of Advanced Nasopharyngeal Cancer
Authors: Xuan-Ping Lu, An-Chih Chen, Ming-Chi Wu, Hsien-Chun Tseng, Pan-Fu Kao
Journal: Clinical Nuclear Medicine (2023)

Abstract A 79-year-old man with nasopharyngeal cancer (NPC) presented with diplopia symptom and a history of diabetes mellitus was referred for an FDG PET/CT scan to determine the pretreatment staging. The FDG PET/CT scan revealed NPC with skull base invasion and decreased FDG uptake at the left striatum. A review of his clinical history and a brain MRI conducted 5 months ago confirmed a previous diagnosis of left hyperglycemic hemichorea. In this NPC patient with inadequate blood sugar control, unilateral striatum hypometabolism may persist for up to 5 months after the initial clinical symptoms.
SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer
Authors: Charles M. Rudin, Stephen V. Liu, Ross A. Soo, Shun Lu, Min Hee Hong, Jong-Seok Lee, Maciej Bryl, Daphne W. Dumoulin, Achim Rittmeyer, Chao-Hua Chiu, Ozgur Ozyilkan, Melissa Johnson, Alejandro Navarro, Silvia Novello, Yuichi Ozawa, Sammi Hiu Tam, Namrata S. Patil, Xiaohui Wen, Meilin Huang, Tien Hoang, Raymond Meng, Martin Reck
Journal: Journal of Clinical Oncology (2023)

The phase III SKYSCRAPER-02 study determined whether the benefits of atezolizumab plus carboplatin and etoposide (CE) could be enhanced by the addition of tiragolumab in untreated extensive-stage small-cell lung cancer (ES-SCLC). We report final progression-free survival (PFS) and overall survival (OS) analyses.
Elevated 68Ga-FAPI-04 Activity Due to Staphylococcus aureus Intracranial Infection
Authors: Zeyu Zhang, Wenli Hou, Guixia Pan, Changjing Zuo, Chao Cheng
Journal: Clinical Nuclear Medicine (2023)

Abstract A 37-year-old man was admitted to our hospital after experiencing syncope. An MRI of his head revealed multiple foci of abnormal signal, which could potentially be metastases. The patient then underwent a 68 Ga-FAPI-04 PET/MRI examination, which revealed multiple FAPI-avid foci in the brain. Upon analyzing the cerebrospinal fluid, it was found that the patient had a Staphylococcus aureus infection. The results suggest that 68 Ga-FAPI-04 PET has the potential to be a valuable tool in the visualization of intracranial infectious lesions.
Diagnostic accuracy of AGILE 3+ score for advanced fibrosis in patients with NAFLD: A systematic review and meta-analysis
Authors: Andrea Dalbeni, Rosa Lombardi, Matteus Henrique, Mirko Zoncapè, Grazia Pennisi, Salvatore Petta, Ryosuke Tateishi, Caglayan Keklikkiran, Antonio Colecchia, David Sacerdoti, Alessandro Mantovani, Federico Ravaioli
Journal: Hepatology (2023)

Background and Aims: A simple non-invasive score, the Agile3+ score, combining liver stiffness measurement (LSM), aspartate aminotransferase/alanine aminotransferase ratio, platelet count, diabetes status, sex, and age, has been proposed for identification of advanced fibrosis in patients with suspected non-alcoholic fatty liver disease (NAFLD). We performed a systematic review and meta-analysis of observational studies to evaluate the diagnostic accuracy of the Agile 3+ score in identifying patients with NAFLD and advanced fibrosis. Recently, an International consensus changed the nomenclature of NAFLD into metabolic-associated steatotic liver disease (MASLD), so currently, the two terms are interchangeable. Methods: We systematically searched MEDLINE, Ovid Embase, Scopus, and Cochrane Library electronic databases for full-text published articles in any language from the inception to the 24th of April 2023. We included original articles reporting data on the sensitivity and specificity of the Agile 3+ score, according to previously described rule-out (≤0.451) and rule-in (≥0.679) cut-offs. Results: We included 6 observational studies (total 6955 participants) with biopsy-proven NAFLD (mean age 53 [SE 4] years, mean BMI 30.9 [SE 2.3] Kg/m2, 54.0% men, prevalence of diabetes 59.6%). The pooled prevalence of advanced fibrosis (≥F3) was 42.1%. By the rule-out cut-off, the overall sensitivity and specificity were 88% (95%CI 81-93%; I2=89.2%) and 65% (95%CI 54-75%; I2=97.6%), respectively. By the rule-in cut-off, the overall sensitivity and specificity were 68% (95%CI 57-78%; I2=91.1%) and 87% (95%CI 80-92%; I2=96.7%), respectively. Meta-regression analyses reported that the diagnostic accuracy was partly mediated by age (p<0.01), BMI (p<0.01), and, although not statistically significant, sex (p=0.06). Conclusion: Our systematic review and meta-analysis suggest that Agile3+ accurately diagnoses NAFLD with advanced fibrosis and can identify patients eligible for biopsy and emerging pharmacotherapies. Export
LRH-1 agonist DLPC through STAT6 promotes macrophage polarization and prevents parenteral nutrition-associated cholestasis in mice
Authors: Swati Ghosh, Michael W. Devereaux, Cuining Liu, Ronald J. Sokol
Journal: Hepatology (2023)

Background and Aims: Parenteral nutrition-associated cholestasis (PNAC) is an important complication in patients with intestinal failure with reduced LRH-1 expression. Here, we hypothesized that LRH-1 activation by its agonist, dilauroylphosphatidylcholine (DLPC), would trigger signal transducer and activator of transcription 6 (STAT6) signaling and hepatic macrophage polarization that would mediate hepatic protection in PNAC. Approach and Results: PNAC mouse model (oral DSSx4d followed by PNx14d; DSS-PN) was treated with LRH-1 agonist DLPC (30 mg/kg/day) intravenously. DLPC treatment prevented liver injury and cholestasis while inducing hepatic mRNA expression of Nr5a2 (nuclear receptor subfamily 5 group A member 2), Abcb11 (ATP binding cassette subfamily B member 11), Abcg5 (ATP-binding cassette [ABC] transporters subfamily G member 5), Abcg8 (ATP-binding cassette [ABC] transporters subfamily G member 8), nuclear receptor subfamily 0, and ATP-binding cassette subfamily C member 2 ( Abcc2) mRNA, all of which were reduced in PNAC mice. To determine the mechanism of the DLPC effect, we performed RNA-sequencing analysis of the liver from Chow, DSS-PN, and DSS-PN/DLPC mice, which revealed DLPC upregulation of the anti-inflammatory STAT6 pathway. In intrahepatic mononuclear cells or bone-marrow derived macrophages (BMDM) from PNAC mice, DLPC treatment prevented upregulation of pro-inflammatory (M1) genes, suppressed activation of NFκB and induced phosphorylation of STAT6 and its target genes, indicating M2 macrophage polarization. In vitro, incubation of DLPC with cultured macrophages showed that the increased Il-1b and Tnf induced by exposure to lipopolysaccharides or phytosterols was reduced significantly, which was associated with increased STAT6 binding to promoters of its target genes. Suppression of STAT6 expression by siRNA in THP-1 cells exposed to lipopolysaccharides, phytosterols, or both resulted in enhanced elevation of IL-1B mRNA expression. Furthermore, the protective effect of DLPC in THP-1 cells was abrogated by STAT6 siRNA. Conclusions: These results indicate that activation of LRH-1 by DLPC may protect from PNAC liver injury through STAT6-mediated macrophage polarization.
Prevalence and characteristics of hepatitis delta virus infection in patients with hepatitis B in the United States: An analysis of the All-Payer Claims Database
Authors: Robert G. Gish, Ira M. Jacobson, Joseph K. Lim, Christine Waters-Banker, Ankita Kaushik, Chong Kim, Anissa Cyhaniuk, Robert J. Wong
Journal: Hepatology (2023)

Background and Aims: HDV leads to the most severe form of viral hepatitis; however, the prevalence of HDV is not well understood. Using real-world data from the All-Payer Claims Database, this study estimates the prevalence of HBV/HDV infection among the chronic HBV population and describes patient/clinical characteristics for adults with HBV/HDV infection in the United States. Approach and Results: Adults (≥18 years) with ≥1 inpatient claim or ≥2 outpatient claims for HDV infection or HBV in the All-Payer Claims Database from January 1, 2014, to December 31, 2020, were identified. HDV prevalence was calculated as the proportion of patients with HBV/HDV infection among total patients with HBV infection. Patient characteristics, socioeconomic status, advanced liver complications (eg, cirrhosis, HCC), and comorbidities were assessed. A total of 6719 patients were diagnosed with HBV/HDV among 144,975 with HBV and 12 months of continuous data, for a prevalence of 4.6%. At diagnosis, 31.7% of patients with HBV/HDV had advanced liver complications, including compensated cirrhosis (16.3%) and decompensated cirrhosis (10.4%). Diabetes (50.5%), hypertension (49.8%), and HIV infection (30.9%) were the top 3 comorbidities. Conclusions: In a large database capturing approximately 80% of the US-insured population, HBV/HDV infection prevalence was 4.6% among adults infected with HBV. Patients infected with HDV had high rates of baseline liver complications and other comorbidities at the time of diagnosis, suggesting potentially delayed diagnosis and/or treatment. Earlier identification of HBV/HDV infection among the population with HBV may provide opportunities to improve linkage to care and treatment, thereby reducing the risk of liver-related morbidity and mortality.
Evaluation of terlipressin-related patient outcomes in hepatorenal syndrome-acute kidney injury using point-of-care echocardiography
Authors: Madhumita Premkumar, Kamal Kajal, K. Rajender Reddy, Manhal Izzy, Anand V. Kulkarni, Ajay Kumar Duseja, K. Bhupendra Sihag, Smita Divyaveer, Ankur Gupta, Sunil Taneja, Arka De, Nipun Verma, Sahaj Rathi, Harish Bhujade, Sreedhara B. Chaluvashetty, Akash Roy, Vishesh Kumar, Vuppada Siddhartha, Virendra Singh, Ajay Bahl
Journal: Hepatology (2023)

Background & Aims: Treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI), with terlipressin and albumin, provides survival benefit, but may be associated with cardiopulmonary complications. We analysed the predictors of terlipressin response and mortality using point-of-care echocardiography (POC-Echo), cardiac and renal biomarkers. Approach: Between December 2021 and January 2023, patients with HRS-AKI were assessed with POC-Echo and lung ultrasound within 6h of admission, at the time of starting terlipressin(48h), and at 72h. Volume expansion was done with 20% albumin, followed by terlipressin infusion. Clinical data, POC-Echo data, and serum biomarkers were prospectively collected. Cirrhotic Cardiomyopathy(CCM) was defined per 2020 criteria. Results: One hundred and forty patients were enrolled [84% men, 59% alcohol-associated disease, mean MELDNa-25±standard deviation(SD) 5.6]. Median daily dose of infused terlipressin was 4.3(interquartile range:3.9-4.6)mg/day; mean duration-6.4± SD-1.9 days; complete response was in 62% and partial response in 11%. Overall mortality was 14% and 16% at 30 and 90 days, respectively. Cut-offs for prediction of terlipressin nonresponse were cardiac variables-[E/e'>12.5(indicating increased left filling pressures, C-statistic-0.774), e' velocity<7 cm/s (indicating impaired relaxation; C-statistic-0.791), >20.5% reduction in cardiac index at 72h(C-statistic-0.885); p<0.001] and pre-treatment biomarkers (Cystatin C>2.2 mg/l, C-statistic-0.640 and NT-ProBNP>350 pg/mL, C-statistic-0.655;p<0.050). About 6% of all HRS-AKI patients and 26% of patients with CCM had pulmonary edema. Presence of CCM(aHR1.9;CI-1.8-4.5,p=0.009) and terlipressin nonresponse (aHR 5.2;CI-2.2-12.2, p<0.001) were predictors of mortality independent of age, gender, obesity, DM-2, etiology and baseline creatinine Conclusions: Cirrhotic cardiomyopathy and reduction in cardiac index, reliably predict terlipressin non-response. CCM is independently associated with poor survival in HRS-AKI. Export
A multicellular liver organoid model for investigating hepatitis C virus infection and nonalcoholic fatty liver disease progression
Authors: Jaeseo Lee, Dayeon Gil, Hyeyeon Park, Youngsun Lee, Seon Ju Mun, Yongbo Shin, Eunji Jo, Marc P. Windisch, Jung-Hyun Kim, Myung Jin Son
Journal: Hepatology (2023)

HCV infection can be successfully managed with antiviral therapies; however, progression to chronic liver disease states, including NAFLD, is common. There is currently no reliable in vitro model for investigating host-viral interactions underlying the link between HCV and NAFLD; although liver organoids (LOs) show promise, they currently lack nonparenchymal cells, which are key to modeling disease progression.
Abnormal biomarkers predict complex FAS or FADD defects missed by exome sequencing
Authors: Anne Rensing-Ehl, Myriam Ricarda Lorenz, Marita Führer, Wolfgang Willenbacher, Ella Willenbacher, Sieghart Sopper, Mario Abinun, Maria Elena Maccari, Christoph König, Pauline Haegele, Sebastian Fuchs, Carla Castro, Patrick Kury, Olivier Pelle, Christian Klemann, Maximilian Heeg, Julian Thalhammer, Oliver Wegehaupt, Marco Fischer, Sigune Goldacker, Björn Schulte, Saskia Biskup, Philippe Chatelain, Volker Schuster, Klaus Warnatz, Bodo Grimbacher, Andrea Meinhardt, Dirk Holzinger, Prasad Thomas Oommen, Tanja Hinze, Holger Hebart, Karlheinz Seeger, Kai Lehmberg, Timothy Ronan Leahy, Alexander Claviez, Simon Vieth, Freimut H. Schilling, Ilka Fuchs, Miriam Groß, Frederic Rieux-Laucat, Aude Magerus, Carsten Speckmann, Klaus Schwarz, Stephan Ehl
Journal: Journal of Allergy and Clinical Immunology (2023)
In vivo evolution to high-level cefiderocol resistance of NDM-1–producing Klebsiella pneumoniae, followed by intra-hospital cross-transmission
Authors: Carlo Tascini, Marco Coppi, Alberto Antonelli, Claudia Niccolai, Andrea Bartolini, Davide Pecori, Assunta Sartor, Tommaso Giani, Gian Maria Rossolini
Journal: Clinical Microbiology and Infection (2023)
Loss of p53-DREAM-mediated repression of cell cycle genes as a driver of lymph node metastasis in head and neck cancer
Authors: Kevin Brennan, Almudena Espín-Pérez, Serena Chang, Nikita Bedi, Saumyaa Saumyaa, June Ho Shin, Sylvia K. Plevritis, Olivier Gevaert, John B. Sunwoo, Andrew J. Gentles
Journal: Genome Medicine (2023)

Abstract Background The prognosis for patients with head and neck cancer (HNC) is poor and has improved little in recent decades, partially due to lack of therapeutic options. To identify effective therapeutic targets, we sought to identify molecular pathways that drive metastasis and HNC progression, through large-scale systematic analyses of transcriptomic data. Methods We performed meta-analysis across 29 gene expression studies including 2074 primary HNC biopsies to identify genes and transcriptional pathways associated with survival and lymph node metastasis (LNM). To understand the biological roles of these genes in HNC, we identified their associated cancer pathways, as well as the cell types that express them within HNC tumor microenvironments, by integrating single-cell RNA-seq and bulk RNA-seq from sorted cell populations. Results Patient survival-associated genes were heterogenous and included drivers of diverse tumor biological processes: these included tumor-intrinsic processes such as epithelial dedifferentiation and epithelial to mesenchymal transition, as well as tumor microenvironmental factors such as T cell-mediated immunity and cancer-associated fibroblast activity. Unexpectedly, LNM-associated genes were almost universally associated with epithelial dedifferentiation within malignant cells. Genes negatively associated with LNM consisted of regulators of squamous epithelial differentiation that are expressed within well-differentiated malignant cells, while those positively associated with LNM represented cell cycle regulators that are normally repressed by the p53-DREAM pathway. These pro-LNM genes are overexpressed in proliferating malignant cells of TP53 mutated and HPV + ve HNCs and are strongly associated with stemness, suggesting that they represent markers of pre-metastatic cancer stem-like cells. LNM-associated genes are deregulated in high-grade oral precancerous lesions, and deregulated further in primary HNCs with advancing tumor grade and deregulated further still in lymph node metastases. Conclusions In HNC, patient survival is affected by multiple biological processes and is strongly influenced by the tumor immune and stromal microenvironments. In contrast, LNM appears to be driven primarily by malignant cell plasticity, characterized by epithelial dedifferentiation coupled with EMT-independent proliferation and stemness. Our findings postulate that LNM is initially caused by loss of p53-DREAM-mediated repression of cell cycle genes during early tumorigenesis.